Utility of different outcome measures for the nitroglycerin model of migraine in mice

详细信息    查看全文

• 作者：Sá ; ndor Farkas^a ; ^b ; ^{farkass1@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Kata Bö ; lcskei^a ; ^c ; ^{kata.bolcskei@aok.pte.hu" class="auth_mail" title="E-mail the corresponding author} ; Adrienn Markovics^a ; ^c ; ^{adri.markovics@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Anita Varga^d ; ^{anivarga@richter.hu" class="auth_mail" title="E-mail the corresponding author} ; Á ; gnes Kis-Varga^d ; ^{i.kisvarga@richter.hu" class="auth_mail" title="E-mail the corresponding author} ; Viktó ; ria Kormos^a ; ^{viktoria.kormos@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Balá ; zs Gaszner^e ; ^{balazs.b.gaszner@aok.pte.hu" class="auth_mail" title="E-mail the corresponding author} ; Csilla Horvá ; th^a ; ^d ; ^{horvathcsiti@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Bernadett Tuka^f ; ^g ; ^{tukabernadett@googlemail.com" class="auth_mail" title="E-mail the corresponding author} ; Já ; nos Tajti^f ; ^{tajti.janos@med.u-szeged.hu" class="auth_mail" title="E-mail the corresponding author} ; Zsuzsanna Helyes^a ; ^c ; ^h ; ^{zsuzsanna.helyes@aok.pte.hu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：5-HT ; serotonin ; CGRP ; calcitonin gene related peptide ; NTG ; nitroglycerin ; NO ; nitrogen monoxide ; nNOS ; neuronal nitrogen monoxide synthase ; TNC ; trigeminal nucleus caudalis ; TRP ; transient receptor potential ; TRG ; trigeminal ganglion ; PBS ; phosphate-buffered saline ; PBS-T ; Triton-X containing PBS ; DAB ; diaminobenzidine ; sGC ; soluble guanylate cyclase ; cGMP ; cyclic guanosine monophosphate ; i.p. ; intraperitoneal ; i.v. ; intravenous ; s.c. ; subcutaneous
• 刊名：Journal of Pharmacological and Toxicological Methods
• 出版年：2016
• 出版时间：January-February 2016
• 年：2016
• 卷：77
• 期：Complete
• 页码：33-44
• 全文大小：895 K

文摘

Majority of the work for establishing nitroglycerin (NTG)-induced migraine models in animals was done in rats, though recently some studies in mice were also reported. Different special formulations of NTG were investigated in various studies; however, NTG treated groups were often compared to simple saline treated control groups. The aim of the present studies was to critically assess the utility of a panel of potential outcome measures in mice by revisiting previous findings and investigating endpoints that have not been tested in mice yet.

Methods

We investigated two NTG formulations, Nitrolingual and Nitro Pohl, at an intraperitoneal dose of 10 mg/kg, in comparison with relevant vehicle controls, and evaluated the following outcome measures: light aversive behaviour, cranial blood perfusion by laser Doppler imaging, number of c-Fos- and neuronal nitrogen monoxide synthase (nNOS)-immunoreactive neurons in the trigeminal nucleus caudalis (TNC) and trigeminal ganglia, thermal hyperalgesia and tactile allodynia of the hind paw and orofacial pain hypersensitivity.

Results

We could not confirm previous reports of significant NTG-induced changes in light aversion and cranial blood perfusion of mice but we observed considerable effects elicited by the vehicle of Nitrolingual. In contrast, the vehicle of Nitro Pohl was apparently inert. Increased c-Fos expression in the TNC, thermal hyperalgesia, tactile allodynia and orofacial hypersensitivity were apparently good endpoints in mice that were increased by NTG-administration. The NTG-induced increase in c-Fos expression was prevented by topiramate but not by sumatriptan treatment. However, the NTG-induced orofacial hypersensitivity was dose dependently attenuated by sumatriptan.

Discussion

Our results pointed to utilisable NTG formulations and outcome measures for NTG-induced migraine models in mice. Pending further cross-validation with positive and negative control drugs in these mouse models and in the human NTG models of migraine, these tests might be valuable translational research tools for development of new anti-migraine drugs.